DESCRIPTION (Investigator's Abstract): The essentiality of dietary n-3 fatty acids remains an unresolved issue in human nutrition. The high content of docosahexaenoic acid (22:6n3 or DHA) in the phospholipids of retina and cerebral cortex suggested an important role in photoreceptor and neuronal membrane functions. We have observed significant effects of n-3 fatty acid deprivation in rhesus monkeys during combined prenatal and postnatal development. DHA levels in retinal and brain phospholipids were greatly reduced, and visual acuity development and electroretinograms were abnormal. Effects on the electroretinogram (ERG) were not reversible by refeeding with fish oil or pure DHA at 10 months or older. Behavioral effects included large increases in fluid intake (polydipsia), increased stereotyped behaviors, and persevering errors in a learning task. Monkeys deprived only postnatally showed similar ERG changes and polydipsia. They propose new studies with rhesus monkeys to investigate some remaining critical questions about the effects of dietary n-3 fatty acid deficiency: (1) What dietary n-3 fatty acid is optimal for functional development? Should infants receive preformed DHA or can they synthesize sufficient DHA from dietary alpha-linolenic acid? (2) What minimum amount of dietary n-3 fatty acids is needed to promote normal postnatal development? Are sufficient quantities provided by some widely-used human infant formulas? (3) Can effects of the deficiency on retinal function be reversed by refeeding with n-3 fatty acids at ages earlier than 10 months, and can a critical period be defined? (4) Can effects of low dietary n-3 fatty acids be separated from those of high n-3 fatty acids? (5) Does n-3 fatty acid deficiency affect sensory systems other than visual; and does the deficiency affect complex cognitive abilities including learning and memory? (6) How does the deficiency alter phospholipid molecular species composition, activity of key enzymes in brain phospholipid metabolism, vitamin E and peroxide levels in plasma and tissues, and lipofuscin accumulation in the retina and other tissues? These studies will help to determine nutritional needs for n-3 fatty acids during development and to establish the role of these fatty acids in neural functioning. The research has important implications for optimum diets of pregnant and lactating women as well as infants and children.